TROPONINEETROPONINOSI

AlessandraChinagliaOspedaleMariaVi9oria

ASLTO2,Torino

Troponina

Troponinosi

?

NonècardiospecificaNonèsinonimodiIMA

NonèimportanteIlpazientenonècardiologico

Latroponinaècardiospecifica?

LetroponinecardiachesonocomponenEdell’apparatocontraGledeimiociE

TroponinaTeI:ada9earilevareundannomiocardicoperchèespressecomeisoformecardiospecifiche

Aumentasolosecondariamenteanecrosimiocardica?

ischemic,inflammatory,infiltra:ve,directtrauma,andtoxiccauses

1%annualturnoverattheageof25to0.45%attheageof75years15minofmildischemia:developmentoftroponinIdegrada:onproducts

Reversibleinjurytothemyocytemembrane:myocardialstretch,ischemia.

Agewall,EuropeanHeartJournal(2011)32,404–411

IMA=TROPONINA?

Troponina:goldstandardperladiagnosidiinfartomiocardicoacutoTipicacurvadellatroponinasoprail99°percenEledellapopolazione

IMA:necrosimiocardicadovutaadischemia

TROPONINAnonèsufficienteperIMA

TROPONINAènecessariaperIMA

IncrementodellatroponinanonèsinonimodieventocoronaricoacutoomalaGa

cardiaca

E’sinonimodimalaSacoronarica?

Mahajan,CirculaEon.2011;124:2350-2354

Qualeu:litànell’IMA?

Mahajan,CirculaEon.2011;124:2350-2354

CarenzadiO2almiocardioperaumentaterichiesteeridoXoapporto(ipossia,ipotensione,anemia):IMA:poII

DannomiocardicodireXodaendotossine,citochine,radicalitossici,

Dannomiocardiconeuromediato(adrenalina)

Stretchventricolare,strainventricolodestro

StenosiaorEca

ScompensocardiacoEmboliapolmonare

Fibrillazioneatriale

deFilippi,JAMA2003;290:353

Sepsi

Sepsi Insufficienzarenale

Stroke Polmonite

HusseinJACC.2013December3;62(22):2112–2120

Melki,JACC2015;65:1655–64

Melki,JACC2015;65:1655–64

Melki,JACC2015;65:1655–64

Qualsiasiincrementoditroponinaanchesenonèsinonimodisindromecoronaricaacutarappresentaunaanomaliacardiacaehaunvaloreprognos:co.

Troponinosi:falsiposi:vi?

……..manonindicailmeccanismoso9ostante

Scompensocardiacoacuto

Ilcardiologoèsemprecoinvolto?

Valoreassolutodellatroponina

Mahajan,CirculaEon.2011;124:2350-2354

Tipodicurvadellatroponina

Xue,EurJHeartFail.2011Jan;13(1):37-42

Scompensocardiacoacuto

Conclusioni

Unincrementoditroponina:•  E’sempreunimportantemarkerdigravitàdelpaziente•  E’sempresinonimodidannomiocardico•  E’condizionenecessariamanonsufficienteperladiagnosidiIMA•  E’unfaXoreprognos:camentenega:vonell’IMA,nellealtre

causecardiacheenoncardiachedidannomiocardico•  IlvaloreassolutoelevatoèunacaraXeris:caprognos:canega:va•  LapresenzadiunacurvaèunacaraXeris:caprognos:canega:va•  Nonfornisceindicazionisulmeccanismodinecrosi/ischemia/

dannomiocardicochepuòsoloessereiden:ficatoclinicamente

TherearenoguidelinestotreatpaEentswithelevatedcTnlevelsandnocoronarydisease.ThecurrentstrategyoftreatmentofpaEentswithelevatedtroponinandnon-ACSinvolvestreaEngtheunderlyingcauses.

Agewall,EuropeanHeartJournal(2011)32,404–411

Insufficienzarenale

•  Cos’èlatroponina•  Perchélatroviamonelsangue•  DiagnosidiIMA•  IeII:po•  AltopotereprediSvnegtaivo•  Significatoprognos:co•  Altrecondizionicardiache•  Significatoprognos:co•  Condizioninoncardiache•  Significatoprognos:co•  Importanzadelvaloressoluto•  Importanzadelladinamica•  Importanzadellaclinica

•  Approximately5%to8%oftroponinIandTisunboundin•  thecytosol(11)oraspartofanearlyreleasablepool(12).•  Thisunboundpooloftroponinisreleasedfirst,regardlessof•  thecauseofthetypeofmyocyteinjury(Table1).Itwould•  beexpectedthatifthereisreleasefromthispoolthatthe•  troponinwouldbereleasedquicklyandthatbloodlevels•  wouldfallwithrapidwashout.Thehalf-lifeoftroponinT•  andtroponinIinthebloodisabout2h(13).Rapidriseand•  fallwithin24hmaythereforebeconsistentwithreleaseof•  thispoolandreversiblemyocytedamageratherthanmyocyte•  necrosiswherea:me-dependentfalloveralonger•  period(4to10days)wouldbeexpectedbecauseofgradual•  degrada:onofmyofibrilsandreleaseofthetroponincomplex•  (11).Theprolongedhalf-lifeseeninACSmaybedue•  tocon:nuedbreakdownofthecontrac:leproteins.

Insufficienzarenalethesourceofthetroponinisclearlyofcardiacorigin.TheexactdegreeofdependenceoftroponinIorTonrenalfunc:onfortheirclearanceremainsunknown;however,itisincreasinglyheldthatalargepercentageofcircula:ngtroponinsinpa:entswithchronickidneydiseasemaybeexplainedbyunderlyingstructuralheartdiseaseand/ordirecttoxiceffectsofrenalfailureonthemyocardium,ratherthananyeffectontroponinclearance;52basedonthemolecularweightoftroponin,itsclearanceshouldbelessdependentonglomerularfiltra:on.whenelevatedinapa:entwithrenalfailure,troponinsaremarkedlyprognos:c.Thus,atroponinabovethe99thpercen:leinanHFpa:entwithrenalfailureshouldnotbesimplydiscardedasa‘falseposi:ve’duetoreducedclearance.WhiletroponinTappearstobemorelikelytobemeasurableorfranklyelevatedinpa:entswithrenalfailurecomparedwithtroponinI,withthegrowinguseofhighlysensi:vemethodsfortroponintes:ng,itremainstobeseenifthisdifferencebetweentroponinTandIinrenalpa:entswillpersist.

Scompensocardiacoacuto

Inacuteheartfailure†Thetroponinvalueshouldbepromptlymeasured,withthegoaltoconfirmorexcludeTypeIMIastheprecipitant†AnelevatedtroponinshouldalwaysbeinterpretedwithahighlevelofsuspicionforTypeIMI,par:cularlyinthecontextofariseorfallofthemarker,typicalsymptoms,orsignsofischaemiaonnon-invasivetes:ngorevidencefornewlossofmyocardialfunc:on†TroponinvaluesmayriseintheacuteseSngandfallduringtreatmentofHFinhospitalizedpa:ents.PaXernsoftroponinreleasecannotbeusedtoinferacoronaryvs.non-coronarymechanismandnoassump:onsregardingthepresenceorabsenceofanacutecoronarysyndromeshouldbemade†Troponinvaluesabovethe99thpercen:lehaveconsistentlybeenassociatedwithahighlikelihoodforanadverseoutcomeinacuteHFindependentofincidentMI.Higherconcentra:onsareassociatedwithaworseoutcome†BesidesappropriatetreatmentforTypeIMI,dataarelackingaboutspecifictherapeu:cinterven:onfortroponinvaluesabovethe99thpercen:leinacuteHF

Cardiactroponinsarecomponentsofthecontractualapparatusincardiacmyocytesandareexpressedexclusivelyintheheart.Anumberofnonischemiccondi:onsincludingmyocardi:s,pulmonaryembolism,acuteandchronicheartfailure,andsepsismaybeassociatedwithelevatedtroponinlevels(1,2),althoughtheymayincludesupply–demandimbalanceandthusatleastsomeelementofischemia.Eleva:onoftroponinswiththesecondi:onsisassociatedwithworseprognosisthantheprognosisforpa:entswithouttroponineleva:ons,andtheprognosisisusuallyworsethanthatforpa:entswithtroponineleva:onwithacutecoronarysyndromes(ACS)(

White,JACC2011

Incrementoditroponinadacausenoncardiache

1)  CarenzadiO2almiocardioperaumentaterichieste(tachicardia,febbre)eridoXoapporto(ipossiaperinsufficienzarespiratoria,disfunzionemicrovascolare,ipotensione,anemia):IMA:poII

2)  DannomiocardicodireXodaendotossine,citochine,radicalitossici.

Insufficienzarenalethesourceofthetroponinisclearlyofcardiacorigin.TheexactdegreeofdependenceoftroponinIorTonrenalfunc:onfortheirclearanceremainsunknown;however,itisincreasinglyheldthatalargepercentageofcircula:ngtroponinsinpa:entswithchronickidneydiseasemaybeexplainedbyunderlyingstructuralheartdiseaseand/ordirecttoxiceffectsofrenalfailureonthemyocardium,ratherthananyeffectontroponinclearance;52basedonthemolecularweightoftroponin,itsclearanceshouldbelessdependentonglomerularfiltra:on.whenelevatedinapa:entwithrenalfailure,troponinsaremarkedlyprognos:c.Thus,atroponinabovethe99thpercen:leinanHFpa:entwithrenalfailureshouldnotbesimplydiscardedasa‘falseposi:ve’duetoreducedclearance.WhiletroponinTappearstobemorelikelytobemeasurableorfranklyelevatedinpa:entswithrenalfailurecomparedwithtroponinI,withthegrowinguseofhighlysensi:vemethodsfortroponintes:ng,itremainstobeseenifthisdifferencebetweentroponinTandIinrenalpa:entswillpersist.

Scompensocardiacoacuto

Inacuteheartfailure†Thetroponinvalueshouldbepromptlymeasured,withthegoaltoconfirmorexcludeTypeIMIastheprecipitant†AnelevatedtroponinshouldalwaysbeinterpretedwithahighlevelofsuspicionforTypeIMI,par:cularlyinthecontextofariseorfallofthemarker,typicalsymptoms,orsignsofischaemiaonnon-invasivetes:ngorevidencefornewlossofmyocardialfunc:on†TroponinvaluesmayriseintheacuteseSngandfallduringtreatmentofHFinhospitalizedpa:ents.PaXernsoftroponinreleasecannotbeusedtoinferacoronaryvs.non-coronarymechanismandnoassump:onsregardingthepresenceorabsenceofanacutecoronarysyndromeshouldbemade†Troponinvaluesabovethe99thpercen:lehaveconsistentlybeenassociatedwithahighlikelihoodforanadverseoutcomeinacuteHFindependentofincidentMI.Higherconcentra:onsareassociatedwithaworseoutcome†BesidesappropriatetreatmentforTypeIMI,dataarelackingaboutspecifictherapeu:cinterven:onfortroponinvaluesabovethe99thpercen:leinacuteHF

Cardiactroponinsarecomponentsofthecontractualapparatusincardiacmyocytesandareexpressedexclusivelyintheheart.Anumberofnonischemiccondi:onsincludingmyocardi:s,pulmonaryembolism,acuteandchronicheartfailure,andsepsismaybeassociatedwithelevatedtroponinlevels(1,2),althoughtheymayincludesupply–demandimbalanceandthusatleastsomeelementofischemia.Eleva:onoftroponinswiththesecondi:onsisassociatedwithworseprognosisthantheprognosisforpa:entswithouttroponineleva:ons,andtheprognosisisusuallyworsethanthatforpa:entswithtroponineleva:onwithacutecoronarysyndromes(ACS)(

White,JACC2011

Qualsiasi enEtà di danno miocardico evidenziatomediante la determinazione delle troponine cardiache,comportaunpeggioramentodellaprognosidelpazienteabreve,medioelungotermine:• Scompenso tropo + BNP + > 12 volte la probabilità dimorte• Stroketropo+mortalitàcirca40%vs13%tropo–• TEPtropo+mortalitàospedalieraècompresatrail30edil50%

L’ampio spe9ro di patologie associate ad un rialzo deivalori di troponina cardiaca è potenzialmente causa diconfusione diagnosEca e genera una grande incertezzaneltra9amentodelpaziente.

•  CardiactroponinIandTarecomponents•  ofthecontrac:leapparatusofmyocardialcellsandare

•  expressedalmostexclusivelyintheheart.

•  Althougheleva:onsof•  thesebiomarkersinthebloodreflectinjuryleadingtonecrosis

•  ofmyocardialcells,theydonotindicatetheunderlyingmechanism.

•  Troponinsshouldbeinterpretedwithinthecontextofthespecificclinicalpresenta:oninwhichtheyaremeasured

•  Inpa:entswithHF,therearenumerouscausesforcircula:ngtroponinconcentra:onsabovethe99thpercen:le,includingcoronaryandnon-coronarymechanisms.

•  Therecogni:onofatroponinthatisabovethe99thpercen:leanditsrisingand/orfallingdoesnotabsolutelyindicatethepresenceofaTypeIMI

•  Withthegrowinguseofhighlysensi:vetroponinmethods,anevenlargerpercentageofHFpa:entswillhavemeasurableorelevatedtroponin